Does denosumab (Prolia) interfere with the efficacy of the influenza vaccine?

Denosumab and Influenza Vaccine Efficacy

Denosumab (Prolia) does not significantly interfere with the efficacy of the influenza vaccine, and patients on denosumab should receive their annual influenza vaccination regardless of timing relative to denosumab administration. 1

Impact of Denosumab on Immune Response

• Denosumab inhibits the receptor activator of nuclear factor κ-Β ligand (RANKL), which has immune system modulatory effects, but current evidence does not indicate that it significantly impairs influenza vaccine response 2
• While denosumab has been associated with a slightly higher incidence of serious adverse events of infections (RR 1.21), particularly ear, nose, and throat infections (RR 2.66) and gastrointestinal infections (RR 1.43), the overall risk for any infection or infection-related mortality is comparable to control groups 2
• Unlike some immunosuppressive medications that significantly impair vaccine response, denosumab has not been specifically identified as an agent that reduces influenza vaccine immunogenicity 1

Influenza Vaccine Efficacy in Context

• Influenza vaccine effectiveness varies by season and population, with efficacy ranging from 70-90% in healthy adults when vaccine strains match circulating viruses 1
• In elderly and immunocompromised individuals, vaccine effectiveness may be lower but still provides important protection against severe complications, hospitalization, and death 1
• The influenza vaccine has been shown to reduce pneumonia by 53%, hospitalization by 50%, and mortality by 68% in meta-analyses, even in higher-risk populations 1

Medications Known to Affect Influenza Vaccine Response

• Several disease-modifying antirheumatic drugs (DMARDs) have been shown to reduce influenza vaccine immunogenicity, including:
  • Rituximab - significantly reduces vaccine response, with optimal timing recommended 6-10 months after rituximab dose 1
  • Methotrexate - reduces vaccine immunogenicity, with evidence supporting temporary discontinuation for 2 weeks after vaccination to improve response 1
  • Abatacept - likely impairs vaccine response, with seroconversion rates as low as 9% compared to 69% in controls in some studies 1
• Other medications have minimal impact on influenza vaccine response:
  • TNF inhibitors and JAK inhibitors - may result in lower antibody titers but similar seroprotection rates compared to controls 1
  • IL-6, IL-12/23, and IL-17 inhibitors (including secukinumab) - do not appear to significantly impact influenza vaccine response 1, 3
  • Low-dose glucocorticoids - have not been shown to impair influenza vaccine response when added to other DMARD therapy 1

Recommendations for Patients on Denosumab

• Patients receiving denosumab should receive the annual influenza vaccine as recommended for their age group 1
• There is no need to time the influenza vaccination in relation to denosumab administration 1
• For patients ≥65 years old, high-dose influenza vaccines may provide better protection, as they have shown improved efficacy in immunocompromised populations 1
• Patients should be counseled that the vaccine may not prevent all cases of influenza but can reduce severity of illness and risk of complications 1

Practical Considerations

• Inactivated influenza vaccines cannot cause influenza infection and are safe for patients on denosumab 1
• Common side effects of influenza vaccination include local injection site reactions lasting up to 2 days and mild systemic symptoms (fever, malaise) lasting 1-2 days 1
• Patients should be advised that optimal protection from influenza vaccination takes approximately 2 weeks to develop 1
• Annual vaccination is necessary due to antigenic drift in circulating influenza viruses and waning immunity 1

Special Considerations

• Patients with a history of severe allergic reaction to eggs or other vaccine components should discuss alternatives with their healthcare provider 1
• Live attenuated influenza vaccine (LAIV) is contraindicated in immunocompromised patients, and only inactivated influenza vaccines should be used 1
• If a patient experiences influenza-like illness despite vaccination, antiviral medications like oseltamivir should be considered, especially if started within 48 hours of symptom onset 4